Describing the Influence of Ball-milling on the Amorphization of Flubendazole Using the PDF and RMC Methods with X-ray Powder Diffraction Data.

Flubendazole (FBZ) is a poorly water-soluble drug, and different methodologies have been proposed to improve its oral bioavailability. Obtaining the amorphous drug phase is an alternative to improve its water solubility. Several techniques for drug amorphization, such as spray drying, lyophilization, melt quenching, solvent-evaporation, and ball milling, can yield various types of structural disorder and possibly render variations in physicochemical properties. Herein, we focus on evaluating the influence of the ball-milling process on the amorphization of FBZ. The characterization of the average global and local structures before, during, and after the milling process is described by sequential Rietveld refinements, pair distribution function analysis, and the Reverse Monte Carlo method. We show that preserving the local structure (nearest molecules) can be responsible for avoiding the fast structure recrystallization commonly observed when using the solvent-evaporation process for the studied drug.

Bioglass 45S5: Structural characterization of short range order and analysis of biocompatibility with adipose-derived mesenchymal stromal cells in vitro and in vivo.

Bioactive glasses have potential applications in the field of regenerative medicine due to their bioactivity that permits interaction with both hard and soft tissues. In the same way, mesenchymal stromal cells (MSCs) have been experimentally tested as part of engineered constructs considering their self-renewal and multipotent capacities. However, to design an association, it is crucial to investigate the physical properties of bioglass 45S5, as well as its biocompatibility. Therefore, we investigated the structural short range order of the stoichiometric 45S5, by obtaining its total structure factors (S(K)) and total pair distribution function G(r). The in vitro compatibility of human MSCs with 45S5 was verified by viability, morphometry and osteoinduction assays, F-actin staining and scanning electron (SEM) analysis. The compatibility outcome was verified through a subcutaneous implantation in a murine model by grafting the 45S5 as a scaffold for allogeneic MSCs. The cell-substrate modulation includes the maintenance of the MSC viability and osteoinduction potential after being exposed to the 45S5 extract. A low spreading during cell adhesion was detected. Both normal actin cytoskeleton organization and nuclei irregularities were observed, besides an increase of hydroxyapatite (HA) depositions around cells. Cells showed satisfactory compatibility patterns when growing over 45S5 for 7, 30 and 90 days. The implant did not show any apparent toxicity for organs, or strong immunogenic reactions, and it was accompanied by a dense capsule formation around the graft. Our results indicate that MSCs can grow in the long term on the 45S5 while maintaining their characteristics. This fact, together with a non-toxicity to animals means that the 45S5 can be implemented in pre-clinical trials aiming MSC's transplantation leading to further bone and tissue repair.